The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

Friday, May 12, 2017

Phenformin improves activity of anti-PD-1

I've talked about Phenformin before:

Here, in 2016: A look at effect of routine meds used by patients when on ipi.... Where though metformin was among many of the meds folks on ipi were taking, "only PPIs were found to have an increased odds of experiencing a partial response or a complete response to ipilimumab on the basis of a case-control analysis". However, one should remember this was 'metformin' NOT phformin.

Here, in 2017: Phenformin (not metformin) can reduce growth of melanoma cells In the first report it notes that thought phenformin has some effect on melanoma cells, metformin has none. The second report notes: Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels.

And now, there's this:

Phenformin inhibits
myeloid-derived suppressor cells and enhances the anti-tumor activity
of PD-1 blockade in melanoma.
Kim, Li, Trousil, et al. J
Invest Dermatol. 2017 Apr 19. Biguanides,
such as the diabetes therapeutics metformin and phenformin, have
demonstrated antitumor activity both in vitro and in vivo. However,
their potential effects on the tumor microenvironment are largely
unknown. Here we report that phenformin selectively inhibits
granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of
tumor bearing mice and ex vivo. Phenformin induces production of
reactive oxygen species in G-MDSC, whereas the antioxidant
N-acetylcysteine attenuates the inhibitory effects of phenformin.
Importantly, co-treatment of phenformin enhances the effect of
anti-PD-1 antibody therapy on inhibiting tumor growth in the BRAF
V600E/PTEN null melanoma mouse model. Combination of phenformin and
anti PD-1 cooperatively induces CD8+ T cell
infiltration and decreases levels of proteins that are critical for
immune suppressive activities of MDSCs. Our findings demonstrate a
selective, inhibitory effect of phenformin on G-MDSCs-driven immune
suppression and support that phenformin improves the anti-tumor
activity of PD-1 blockade immunotherapy in melanoma.
When it comes to myeloid suppressor cells, remember I've posted reports from many sources that note that they stand in the way of a response for many: Markers for response to immunotherapy: Increased eosinophils = good. Increased Myeloid Suppressor cells = not so good.